The adenylate cyclase of Bordetella pertussis organisms is stimulated 100- to 1000-fold in a dose-dependent manner by calf-brain calmodulin. The system has the following properties: 1) The activation is prevented by EGTA and restored by calcium ion. 2) Oxidation of the methionine residues of calmodulin abolishes the ability to activate the cyclase. 3) Trifluoperazine inhibits calmodulin-activated cyclase. 4) A troponin C preparation stimulates the B. pertussis cyclase with less than 0.01 the potency of calmodulin. This is the first report of a calmodulin effect in a prokaryote.